Rounded Turn SLIM Design for High-Resolution Ion Mobility Mass Spectrometry Analysis of Small Molecules

Various rounded turn designs in Structures for Lossless Ion Manipulation (SLIM) were explored via ion trajectory simulations. The optimized design was integrated into a SLIM ion mobility (IM) system coupled with a time-of-flight (TOF) mass spectrometer (MS) for further experimental investigation. The SLIM-TOF IM-MS system was assessed for IM resolution and ion transmission efficiency across a wide <i>m</i>/<i>z</i> range using various RF frequencies and buffer gas combinations. High ion transmission efficiency and high resolution ion mobility (HRIM) separation were achieved for Agilent tune mix ions through a ∼12.8 m serpentine separation path in both nitrogen and helium. In helium, ion transmission for low <i>m</i>/<i>z</i> ions was enhanced at higher RF trapping frequency, enabling the detection of ions with <i>m</i>/<i>z</i> below 50 and all 17 amino acids from a standard mixture. Lossless ion transmission was observed for glycine (<i>m</i>/<i>z</i> 76) in both passthrough and HRIM modes. HRIM resolution was benchmarked using <i>L</i>-isoleucine, <i>L</i>-leucine, and various other isobaric and isomeric metabolites with <i>m</i>/<i>z</i> values of 60-89. This work demonstrates a rounded turn SLIM design that enables HRIM measurements for small molecule analytes, with a particular focus on metabolomics, where IM offers a means to enhance the speed, robustness, and specificity of analytical workflows.